DESCRIPTION: (Adapted from Proposal) The pseudoautosomal region (PAR) of mammals has several features that make it an uniquely important region for study. It is the region of the X and Y chromosome that pairs during meiosis with a resultant crossover that is confined to a region of about 1% of the X chromosome. As a consequence, one cM equals 53 kbp whereas one cM in female meiosis equals 480 kbp for the identical chromosome region. Second, the PAR is contiguous with X chromosomes that undergo inactivation, but the genes in this region appear to escape from inactivation. Whether the escape is a property of the boundary between the sex chromosome and the PAR, or a function of these genes, remains to be determined. Third, X-Y pairing is essential for completion of meiosis and male fertility. A failure of X-Y pairing that results from either a deletion of the region from the X or Y chromosome or a heterologous combination of X and Y chromosomes in interspecific hybrid males leads to an arrest of meiosis at MI. The P.I. has developed a large array of crucial resources for genetically analyzing this region and has obtained important cloned probes to begin the physical analysis. This proposal describes a series of experimental aims to extend the genetic and physical analysis of the PAR with specific interest in identifying the molecular genetic basis for the failure of X-Y pairing, and the resultant meiotic arrest. The P.I. also proposes to examine the distal end of the X chromosome genetic and physical maps to define the boundary of the PAR and the molecular elements that prevent the spread of X inactivation to these genes. In a second group of aims, the P.I. proposes the further development and maintenance of wild-derived mouse resources that will extend and refine the opportunities for genetic analysis. The specific aims are: 1) To develop a set of strain or species specific molecular probes for the PAR and to characterize the molecular features of these probes in genomic DNA. These cloned probes will be used to genetically and physically analyze the PAR. 2) To identify restriction landmarks in the PAR and recover these sequences as probes for analysis. 3) To analyze the distal X chromosome genetic and physical maps of different Mus species to determine the evolutionary patterns of conservation and divergence from the X to the pseudoautosomal regions. 4) To use the PAR genetic markers to follow the segregation of the X-Y pairing phenotype in intersubspecific and interspecific hybrid males to determine whether this trait is determined by dispersed sequences across the PAR or whether a specific locus is responsible. Development and Maintenance of Wild-derived Mouse Resources: 1) To maintain and re-derive the diverse Mus species that are unique to our colony. 2) To maintain and develop special resources using the Mus special materials.